Reflecting on Resmetirom’s Historic FDA Approval for MASH

On March 14, 2024, the US Food and Drug Administration (FDA) made history when it granted accelerated approval to Madrigal Pharmaceuticals’ resmetirom (Rezdiffra), making it the first and only treatment for noncirrhotic nonalcoholic steatohepatitis (NASH), now known as metabolic dysfunction-associated steatohepatitis (MASH).

One year later, resmetirom’s impact on clinical practice and patient care continues to evolve. In recognition of the anniversary of the landmark decision, the latest HCPLive RX Review spotlights a conversation between a trio of subject matter experts reflecting on the past year of having resmetirom as a treatment option for patients, remaining unmet needs in MASH management, and the evolving therapeutic pipeline poised to further transform care.

Estimated to affect more than 30% of the global population, MASLD is the most common chronic liver disease around the world. MASH represents an advanced stage of MASLD and has historically lacked treatment options beyond lifestyle changes with diet and exercise. In the absence of pharmacologic therapies, weight loss served as the cornerstone of disease management.

This changed in March 2024, when resmetirom became the first and only FDA-approved MASH therapeutic, earning accelerated approval for the treatment of noncirrhotic MASH with moderate to advanced fibrosis. Although lifestyle interventions continue to play a pivotal role in MASH care, as the thyroid hormone receptor-beta selective agonist is indicated in conjunction with diet and exercise, they are no longer the only tools available for disease management.

In the opening segment of our 6-part HCPLive RX Review on the 1-year anniversary of resmetirom’s FDA approval and the evolving landscape of MASH management, moderator Jeff McIntyre asks Mazen Noureddin, MD, MHSc, and Juan Pablo Arab, MD, about the clinical impact resmetirom has had since being approved and whether it lived up to the expectations set for it as the first-ever MASH therapeutic.

Noureddin begins by highlighting resmetirom’s “game-changing” impact, citing strong clinical results, guideline updates, and the shift toward noninvasive testing. He notes that patients are seeing benefits and that long-term data continues to support the drug’s efficacy.

Arab expresses agreement, emphasizing that resmetirom has not only improved patient outcomes but also changed how clinicians approach MASH. Previously, primary care providers and endocrinologists were reluctant to screen for at-risk MASH due to a lack of treatment options. Now, with an FDA-approved therapy, he says there is greater urgency in identifying and managing these patients.

Discussing challenges, Arab points to the need for broader screening, improved access to noninvasive tests, and overcoming reimbursement hurdles, additionally stressing that implementing a new treatment requires systemic change across healthcare.

Noureddin adds that while hepatology clinics were well-prepared for resmetirom’s arrival, uptake in gastroenterology practices has been mixed. He sees a need for more education on noninvasive tests and fibrosis staging but says that overall, awareness and access are improving. He remains optimistic about the drug’s future and the potential for combination therapies to further transform MASH treatment.

Moderator:

Jeff McIntyre is the vice president of Liver Health Programs at the Global Liver Institute.

Panelists:

Mazen Noureddin, MD, MHSc, is a professor of medicine and a transplant hepatologist at Houston Methodist and director of the Houston Research Institute.

Juan Pablo Arab, MD, is an associate professor of medicine in the division of gastroenterology, hepatology, and nutrition at Virginia Commonwealth University School of Medicine.

Noureddin has relevant disclosures with Altimmune, Madrigal Pharmaceuticals, Merck, Takeda, Terns, and others. Arab and McIntyre have no relevant disclosures.

References:

1. US Food and Drug Administration. FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease. March 14, 2024. Accessed March 13, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease

2. Brooks, A. Stephen Harrison, MD: Promising Phase 3 Data for Resmetirom in NASH, Fibrosis. HCPLive. February 7, 2024. Accessed March 13, 2025. https://www.hcplive.com/view/stephen-harrison-md-promising-phase-3-data-resmetirom-nash-fibrosis.